Our goal is to determine the anatomical and neurochemical bases of neuronal control of gonadotrophin secretion. The "premium movens" of gonadotrophin secretion is the gonadotrophin hormone releasing hormone (GNRH) produced by a discrete group of hypothalamic neurons. The feed- back effects of estrogens of GNRH release are mediated in part by estrogen sensitive neuronal circuits which control the activity of the GNRH producing neurons. The control of GNRH delivery systems is differently organized in rodent and primates, at least in part because of anatomical differences such as the intranuclear location of both the GNRH producing - and their related estrogen sensitive neurons in primates, as opposed to the internuclear GNRH delivery system in rats where the GNRH neurons are located in the medial preoptic area. The proposed experiments will contribute to the following aims: a) to complete the identification of the primary circuits of estrogen sensitive neurons supporting the GNRH neurons in the rat, b) to pursue the origins of these circuits in the hypothalamus and extrahypothalamic areas, c) to determine the degree of similarity between the internuclear system of GNRH control in the rat and the intranuclear control in the monkey. Electron microscopic double immunostaining combined with degeneration, antero- and retrograde tracer techniques will be employed to answer the following specific questions: 1) What is the anatomical basis of the interactions between the mediobasal hypothalamus GABA-,dopamine-, and opiocortin systems in the rat? 2) What is the interrelationship between GABAergic-, catecholaminergic-, and GNRH-neurons in the rat medial preoptic area? 3) How do mediobasal hypothalamus opioid peptide- containing neurons regulate norepinephrine/epinephrine cells projecting to the mediobasal hypothalamus and medial preoptic ara? 4) Is the catecholaminergic innervation of GNRH neurons in the rhesus monkey analogous to that in the rat? Do monkey GNRH neurons receive direct information from GABAergic progesterone receptor-containing hypothalamic neurons?